Lithium therapy has for many years been adopted for treatment of patients suffering from mania, bipolar disorder and other psychiatric illnesses. Maintenance of lithium ion blood concentration within the therapeutic concentration range of between 0.5 to 1.0 mmol/L within psychiatric patients, generally via administration of lithium ions in the form of lithium carbonate, has been found to be particularly effective in controlling mood in such patients. A difficulty arises however in that the exposure of patients to elevated lithium ion levels (above approximately 1.5 mmol/L) over an extended period contributes to nephrotoxicity and toxicity to the thyroid gland. Acute elevation of physiological lithium levels presents a medical emergency due to nephrotoxicity. It is of course not uncommon for psychiatric patients to either be non-compliant with their lithium medication or to accidentally or intentionally over medicate. For these reasons, and in order to assist medical practitioners in monitoring the effectiveness of lithium therapy in patients, there is a need for simple and cost effective methods by which lithium can be detected and/or for lithium levels to be quantified within biological liquid samples.
Historically lithium levels in serum have been measured by flame emission photometry techniques. In the use of flame emission photometry for sodium and potassium measurement lithium is adopted as the internal standard. Such techniques are modified for lithium measurement with the lithium internal standard being replaced by caesium. Unfortunately, flame emission photometry apparatus using caesium as the internal standard are expensive to acquire and maintain and can be troublesome to operate.
More recently, lithium concentration measurement in biological samples has been conducted by utilising ion selective electrode (ISE) techniques, which involve crown ethers having a core which accommodates the Li+ ion. While early ISE techniques were prone to interferences caused by sodium and other ions present in the test sample, more recent ISE analysers are capable of accurate and precise lithium measurement. Although ISE analysers are less expensive and easier to operate and maintain than flame photometer equipment, other alternative and relatively low cost lithium measurement techniques are desirable.
A number of porphyrin compounds which show high selectivity for metal ions have recently been identified, as for example reported in Richards et al (1) and Tabata et al (2), the disclosures of which are included herein in their entirety by way of reference. Unfortunately, some difficulties have been encountered in utilising the porphyrin compounds identified in the Richards et al and Tabata et al papers in simple and efficient methods for determining the presence of and/or quantifying the levels of lithium in biological liquid samples. In particular, Tabata et al notes that protein reacts with the porphyrin and reduces absorbance, and that as a result serum subjected to the lithium determination method required the removal of protein by use of trichloroacetic acid. The trichloroacetic acid itself then needed to be removed by extraction with diethyl ether. These protein removal steps increase the complexity and cost of the porphyrin based spectrophotometric lithium measurement techniques, effectively precluding the use of the Tabata et al method on automated chemical analysers.
With the above description in mind it is an object of the present invention to provide a method of detecting and/or measuring lithium levels within biological liquid samples which overcome some or all of the above identified problems with prior art techniques. It is also an object of the invention to provide a reagent that can readily be utilised in such techniques. Other objects of the present invention will become apparent from the following detailed description thereof.